2014
DOI: 10.1128/jvi.00643-14
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RIOK3 Is an Adaptor Protein Required for IRF3-Mediated Antiviral Type I Interferon Production

Abstract: IMPORTANCEThe innate immune response, such as the production of type I interferons, acts as the first line of defense, limiting infectious pathogens directly and shaping the adaptive immune response. In this study, we identified RIOK3 as a novel regulator of the antiviral type I interferon pathway. Specifically, we found that RIOK3 physically interacts with TBK1 and IRF3 and bridges the functions between TBK1 and IRF3 in the activation of type I interferon pathway. The identification of a cellular kinase that … Show more

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Cited by 46 publications
(38 citation statements)
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“…In contrast, yeast cells depleted of RIOK-2 do not feature any stage specific cell cycle arrest; however, they show accelerated mitotic exit and a correlated increase in the degradation of the cell cycle regulator cyclin B1 [ 6 ]. Recently, RIOK-3 was shown to be an adapter protein required for NF-κB signaling [ 19 ] and for antiviral immune responses via the type I interferon pathway [ 20 ].…”
Section: Introductionmentioning
confidence: 99%
“…In contrast, yeast cells depleted of RIOK-2 do not feature any stage specific cell cycle arrest; however, they show accelerated mitotic exit and a correlated increase in the degradation of the cell cycle regulator cyclin B1 [ 6 ]. Recently, RIOK-3 was shown to be an adapter protein required for NF-κB signaling [ 19 ] and for antiviral immune responses via the type I interferon pathway [ 20 ].…”
Section: Introductionmentioning
confidence: 99%
“…RIOK3 is a novel regulator of the antiviral type I interferon pathway and plays a crucial role in the antiviral type I interferon pathway. However, type I interferon is involved in the innate immune response which functions as the first line of defense and limits infectious pathogens directly [ 34 ], therefore we predicted that RIOK3-like is related closely to innate immunity. Mitogen-activated protein kinase kinase 6 (MP2K6), a member of the MAPK family which are signal transduction mediators that have been implicated in cell survival and death [ 35 ], is also activated during engagement of the Type I IFN receptor and plays important roles in Type I IFN signaling and generation of IFN responses [ 36 ].…”
Section: Resultsmentioning
confidence: 99%
“…Compared with RIOK-1 and RIOK-2, much less is known about RIOK-3. The function of RIOK-3 is different from those of RIOK-1 and RIOK-2 in human cells, with RIOK-3 controlling tumor cell invasiveness, suppressing the activity of NF-κB and supporting type I-interferon production [13,14,53,54]. Recently, human RIOK-3 was discovered in ribosomal 40S subunit particles [10].…”
Section: Discussionmentioning
confidence: 99%
“…Analyses of RIOK-1 and RIOK-2 in a complex with ATP [6,55] reveal that the putative ATP binding motif, along with the beta strand-three, actually participate in binding ATP and that the Lys (K) located in the beta strand-three is required for this interaction. Site mutation changing the Lys (K) in the beta strand-three to Ala (A) in the ATP binding motifs of RIOK-2 and RIOK-3 in yeast and human cells ablate the ATP binding activity and affect the kinase functions of these enzymes [54,56]. Although the Lys (K) from the ATP binding loop does not directly interact with ATP, it is essential for RIOK-2 to bind with pre-40S subunit to participate in ribosomal biogenesis [56].…”
Section: Discussionmentioning
confidence: 99%